Mesenchymal stem cells (MSCs) are the formative pluripotential blast cells found inter alia in bone marrow, blood, dermis and periosteum that are capable of differentiating into more than one specific type of mesenchymal or connective tissues (i.e. the tissues of the body that support the specialized elements; e.g. adipose, osseous, stroma, cartilaginous, elastic and fibrous connective tissues) depending upon various influences from bioactive factors, such as cytokines. Human mesenchymal stem cells (hMSCs) are reactive with certain monoclonal antibodies, known as SH2, SH3 and SH4. (See U.S. Pat. No. 5,486,359).
Hematopoietic stem cells (HSCs) are the formative pluripotential blast cells found inter alia in bone marrow and peripheral blood that are capable of differentiating into any of the specific types of hematopoietic or blood cells, such as erythrocytes, lymphocytes, macrophages and megakaryocytes. After mobilization of HSCs from bone marrow by administration of certain factors such as G-CSF and GM-CSF and subsequent recovery from peripheral blood, HSCs have also come to be referred to as peripheral blood progenitor cells (PBPCs). Human hematopoietic stem cells (hHSCs) and PBPCs are reactive with certain monoclonal antibodies which are now recognized as being specific for hematopoietic cells, for example, CD34.
Thus, hMSCs and hHSCs are readily distinguishable by their immunospecific profiles and, for the sake of clarity herein, will be referred to, for example, herein as SH2.sup.+ -CD14.sup.- hMSCs or SH2.sup.- -CD14.sup.+ hHSCs as needed.
Human hematopoietic stem cell (hHSC), or peripheral blood progenitor cell (PBPC), transplantation has become an accepted method for dose-intensification in the treatment of several neoplastic diseases..sup.1,2 Various procedures have been used for HHSC mobilization and removal from the circulation by apheresis. At present, most methods exploit the rebound in circulating progenitors that occurs after cytotoxic chemotherapy..sup.3 Together, the short-term administration of either GM-CSF or G-CSF, enhances the yield of hHSC, as measured by the number of CD34.sup.+ cells .sup.4,5,6 which, when used for autografting at .gtoreq.2.5.times.10.sup.6 CD34.sup.+ hHSC/kg recipient, ensures fast hematopoietic recovery..sup.4,5,6
Several mechanisms seem to be involved in the growth factor-mediated release of marrow progenitor cells..sup.7 Among them, it appears that after exposure to G-CSF or GM-CSF, adhesion molecules are shed from the surface of marrow resident primitive multilineage cells, therefore allowing them to enter the circulation.sup.5. This concept, has been strengthened by several observations showing that growth factors (like G-CSF, GM-CSF, IL-3 and SCF) modulate the expression or function of several cytoadhesive molecules on the surface of hematopoietic progenitor cells..sup.8,9 In addition, reports cite that cytokines produce profound morphological and immunohistochemical changes in marrow stroma and in the contiguous extracellular matrix..sup.10,11